A fibronectin-related synthetic peptide, Pro-Ala-Ser-Ser, inhibits fibronectin binding to the cell surface, fibronectin-promoted cell migration in vitro, and cell migration in vivo.

The biological activity of the amino acid sequence consisting of the immediate carboxyl terminus side of the Arg-Gly-Asp-Ser (RGDS) amino acid sequence in the cell-binding domain of intact fibronectin (FN) molecules was examined using synthetic peptides [RGDS, Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), Arg-Gly-Asp-Ser-Pro-Ala-Ser-Ser-Lys-Pro (RGDSPASSKP), Pro-Ala (PA), Pro-Ala-Ser (PAS), Pro-Ala-Ser-Ser (PASS), and Pro-Ala-Ser-Ser-Lys (PASSK)]. These peptides were applied to the primary mesenchyme cells (PMCs) of the sea urchin, Clypeaster japonicus. In vitro immunohistochemistry indicated that the binding of exogenous FN to the PMC surface was inhibited by the peptides RGDSPASSKP and PASS, but not by RGDS, GRGDSP, PA, or PAS. PASS and RGDS introduced into the blastocoel also inhibited PMC migration in vivo. FN-promoted PMC migration in vitro was also inhibited by PASS and RGDS. The present results indicate that the PASS peptide inhibits FN binding to the PMC surface and promotes PMC migration, suggesting that the FN molecule uses the PASS amino acid sequence to bind to the PMC surface and to promote PMC migration in the blastocoel.